tbuckley/cabot-search huggingface dataset:
Hemoadhican, a Tissue Adhesion Hemostatic Material Independent of Blood Coagulation
Authors: Changchang Kong, Shijunyin Chen, Xianjin Wang, Chengtao Hu, Bing Li, Renjie Fu, Jianfa Zhang
Journal: Advanced Healthcare Materials (2023)

Abstract Uncontrolled hemorrhage is a leading cause of death, emphasizing the need for novel hemostatic agents. Here, a novel hemostatic polysaccharide hemoadhican (HD) is screened out by analyzing the rheological properties of screened material mixed blood sludges, which is prepared by mixing polysaccharide granules and whole blood to mimic the coagulation in vitro. HD is produced by a bacterial isolate Paenibacillus sp.1229, and the repeating units of HD are →)‐ α ‐L‐Rhap‐(1→3)‐ β ‐D‐Glcp‐(1→4)[4,6‐ethylidene‐ α ‐D‐Galp‐(1→4)‐ α ‐D‐Glcp‐(1→3)]‐ α ‐D‐Manp‐(1→. Compared to chitosan and celox, HD achieves more effective hemostasis in animal models with mouse and rat femoral arteries, rat carotid arteries, and rabbit femoral arteries. Especially, HD maintains an excellent hemostatic capability in animals with heparin‐induced hemorrhage diathesis. In vitro experiments show HD granules can quickly absorb a small amount of blood component to create a hemophobic blood sludge resistant to high pressure. The blood sludge firmly adheres to damaged tissue and efficiently repels blood. In vitro experiments show that HD does not actively trigger blood coagulation cascade and is independent of blood conditions including heparin treatment. In addition, HD moisturizes wounds and accelerates wound healing, exhibiting excellent biodegradability, and hemocompatibility. The results indicate that HD is a promising hemostatic material for treating traumatic hemorrhages and uncontrollable surgical bleeding.
Identification and characterization of a hepatic IL-13–producing ILC3-like population potentially involved in liver fibrosis
Authors: Jan Raabe, Kim M. Kaiser, Michael ToVinh, Claudia Finnemann, Philipp Lutz, Christoph Hoffmeister, Jenny Bischoff, Felix Goeser, Dominik J. Kaczmarek, Tim R. Glowka, Steffen Manekeller, Arthur Charpentier, Bettina Langhans, Hans Dieter Nischalke, Marieta Toma, Christian P. Strassburg, Ulrich Spengler, Ali T. Abdallah, Benjamin Krämer, Jacob Nattermann
Journal: Hepatology (2023)

Human innate lymphoid cells (ILCs) are critically involved in the modulation of homeostatic and inflammatory processes in various tissues. However, only little is known about the composition of the intrahepatic ILC pool and its potential role in chronic liver disease. Here, we performed a detailed characterization of intrahepatic ILCs in both healthy and fibrotic livers.
In situ delivery of a curcumin-loaded dynamic hydrogel for the treatment of chronic peripheral neuropathy
Authors: Yunfan Kong, Wen Shi, Li Zheng, Dongze Zhang, Xiping Jiang, Bo Liu, Wen Xue, Mitchell Kuss, Yulong Li, Paul L. Sorgen, Bin Duan
Journal: Journal of Controlled Release (2023)
Surgery and proton radiation therapy for pediatric base of skull chordomas: Long-term clinical outcomes for 204 patients
Authors: Myrsini Ioakeim-Ioannidou, Andrzej Niemierko, Daniel W Kim, Athena Tejada, Tobias Urell, Shannon Leahy, Judy Adams, Barbara Fullerton, G Petur Nielsen, Yin P Hung, Angela R Shih, Manuel Patino, Karen Buch, Sandra Rincon, Hilary Kelly, Mary Beth Cunnane, Maria Tolia, Brigitte C Widemann, Mary F Wedekind, Liny John, David Ebb, John H Shin, Gregory Cote, William Curry, Shannon M MacDonald
Journal: Neuro-Oncology (2023)

Abstract Background Data on clinical outcomes for base of skull (BOS) chordomas in the pediatric population is limited. We report patient outcomes after surgery and proton radiotherapy (PRT). Methods Pediatric patients with BOS chordomas were treated with PRT or combined proton/photon approach (proton-based; for most, 80% proton/20% photon) at the Massachusetts General Hospital from 1981 to 2021. Endpoints of interest were overall survival (OS), disease-specific survival, progression-free survival (PFS), freedom from local recurrence (LC), and freedom from distant failure (DC). Results Of 204 patients, median age at diagnosis was 11.1 years (range, 1–21). Chordoma location included 59% upper and/or middle clivus, 36% lower clivus, 4% craniocervical junction, and 1% nasal cavity. Fifteen (7%) received pre-RT chemotherapy. Forty-seven (23%) received PRT, and 157 (77%) received comboRT. Median total dose was 76.7 Gy (RBE) (range, 59.3–83.3). At a median follow-up of 10 years (interquartile range, 5–16 years), 56 recurred. Median OS and PFS were 26 and 25 years, with 5-, 10-, and 20-year OS and PFS rates of 84% and 74%, 78% and 69%, and 64% and 64%, respectively. Multivariable actuarial analyses showed poorly differentiated subtype, radiographical progression prior to RT, larger treatment volume, and lower clivus location to be prognostic factors for worse OS, PFS, and LC. RT was well tolerated at a median follow-up of 9 years (interquartile range, 4–16 years). Side effects included 166 patients (80%) with mild/moderate acute toxicities, 24 (12%) patients with late toxicities, and 4 (2%) who developed secondary radiation-related malignancies. Conclusion This is the largest cohort of BOS chordomas in the literature, pediatric and/or adult. High-dose PRT following surgical resection is effective with low rates of late toxicity.
Maternal obesity driven changes in collagen linearity of breast extracellular matrix induces invasive mammary epithelial cell phenotype
Authors: Jensen N. Amens, Gökhan Bahçecioğlu, Kiera Dwyer, Xiaoshan S. Yue, M. Sharon Stack, Tyvette S. Hilliard, Pinar Zorlutuna
Journal: Biomaterials (2023)
The functional and clinical roles of liquid biopsy in patient-derived models
Authors: Ziqing Zhu, Erya Hu, Hong Shen, Jun Tan, Shan Zeng
Journal: Journal of Hematology & Oncology (2023)

The liquid biopsy includes the detection of circulating tumor cells (CTCs) and CTC clusters in blood, as well as the detection of, cell-free DNA (cfDNA)/circulating tumor DNA (ctDNA) and extracellular vesicles (EVs) in the patient's body fluid. Liquid biopsy has important roles in translational research. But its clinical utility is still under investigation. Newly emerged patient-derived xenograft (PDX) and CTC-derived xenograft (CDX) faithfully recapitulate the genetic and morphological features of the donor patients' tumor and patient-derived organoid (PDO) can mostly mimic tumor growth, tumor microenvironment and its response to drugs. In this review, we describe how the development of these patient-derived models has assisted the studies of CTCs and CTC clusters in terms of tumor biological behavior exploration, genomic analysis, and drug testing, with the help of the latest technology. We then summarize the studies of EVs and cfDNA/ctDNA in PDX and PDO models in early cancer diagnosis, tumor burden monitoring, drug test and response monitoring, and molecular profiling. The challenges faced and future perspectives of research related to liquid biopsy using patient-derived models are also discussed.
Pharmacologic targeting of Nedd8-activating enzyme reinvigorates T-cell responses in lymphoid neoplasia
Authors: Xiaoguang Wang, Canping Chen, Dan Vuong, Sonia Rodriguez-Rodriguez, Vi Lam, Carly Roleder, Jing H. Wang, Swetha Kambhampati Thiruvengadam, Allison Berger, Nathan Pennock, Pallawi Torka, Francisco Hernandez-Ilizaliturri, Tanya Siddiqi, Lili Wang, Zheng Xia, Alexey V. Danilov
Journal: Leukemia (2023)

Abstract Neddylation is a sequential enzyme-based process which regulates the function of E3 Cullin-RING ligase (CRL) and thus degradation of substrate proteins. Here we show that CD8 + T cells are a direct target for therapeutically relevant anti-lymphoma activity of pevonedistat, a Nedd8-activating enzyme (NAE) inhibitor. Pevonedistat-treated patient-derived CD8 + T cells upregulated TNFα and IFNγ and exhibited enhanced cytotoxicity. Pevonedistat induced CD8 + T-cell inflamed microenvironment and delayed tumor progression in A20 syngeneic lymphoma model. This anti-tumor effect lessened when CD8 + T cells lost the ability to engage tumors through MHC class I interactions, achieved either through CD8 + T-cell depletion or genetic knockout of B2M . Meanwhile, loss of UBE2M in tumor did not alter efficacy of pevonedistat. Concurrent blockade of NAE and PD-1 led to enhanced tumor immune infiltration, T-cell activation and chemokine expression and synergistically restricted tumor growth. shRNA-mediated knockdown of HIF-1α, a CRL substrate, abrogated the in vitro effects of pevonedistat, suggesting that NAE inhibition modulates T-cell function in HIF-1α-dependent manner. scRNA-Seq-based clinical analyses in lymphoma patients receiving pevonedistat therapy demonstrated upregulation of interferon response signatures in immune cells. Thus, targeting NAE enhances the inflammatory T-cell state, providing rationale for checkpoint blockade-based combination therapy.
An engineered lamellar bone mimicking full-scale hierarchical architecture for bone regeneration
Authors: Tao Yang, Zhichao Hao, Zhenzhen Wu, Binxin Xu, Jiangchen Liu, Le Fan, Qinmei Wang, Yanshan Li, Dongying Li, Sangzhu Tang, Chuanzi Liu, Weichang Li, Wei Teng
Journal: Bioactive Materials (2023)

Lamellar bone, compactly and ingeniously organized in the hierarchical pattern with 6 ordered scales, is the structural motif of mature bone. Each hierarchical scale exerts an essential role in determining physiological behavior and osteogenic bioactivity of bone. Engineering lamellar bone with full-scale hierarchy remains a longstanding challenge. Herein, using bioskiving and mineralization, we attempt to engineer compact constructs resembling full-scale hierarchy of lamellar bone. Through systematically investigating the effect of mineralization on physicochemical properties and bioactivities of multi-sheeted collagen matrix fabricated by bioskiving, the hierarchical mimicry and hierarchy-property relationship are elucidated. With prolongation of mineralization, hierarchical mimicry and osteogenic bioactivity of constructs are performed in a bidirectional manner, i.e. first rising and then descending, which is supposed to be related with transformation of mineralization mechanism from nonclassical to classical crystallization. Construct mineralized 9 days can accurately mimic each hierarchical scale and efficiently promote osteogenesis. Bioinformatic analysis further reveals that this construct potently activates integrin α5-PI3K/AKT signaling pathway through mechanical and biophysical cues, and thereby repairing critical-sized bone defect. The present study provides a bioinspired strategy for completely resembling complex hierarchy of compact mineralized tissue, and offers a critical research model for in-depth studying the structure-function relationship of bone.
Reply to Timothée Olivier, Kerrington Powell, Vinay Prasad. Lutetium-177-PSMA-617 in Metastatic Castration-resistant Prostate Cancer: Limitations of the VISION Trial. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2022.08.022
Authors: Michael J. Morris, Oliver Sartor, Johann S. de Bono, Karim Fizazi, Scott T. Tagawa
Journal: European Urology (2023)
Targeting tumour-associated macrophages in hodgkin lymphoma using engineered extracellular matrix-mimicking cryogels
Authors: Laura C. Bahlmann, Chang Xue, Allysia A. Chin, Arianna Skirzynska, Joy Lu, Brigitte Thériault, David Uehling, Yulia Yerofeyeva, Rachel Peters, Kela Liu, Jianan Chen, Anne L. Martel, Martin Yaffe, Rima Al-awar, Rashmi S. Goswami, Jarkko Ylanko, David W. Andrews, John Kuruvilla, Rob C. Laister, Molly S. Shoichet
Journal: Biomaterials (2023)
Global incidence of non-alcoholic fatty liver disease: A systematic review and meta-analysis of 63 studies and 1,201,807 persons
Authors: Michael H. Le, David M. Le, Thomas C. Baez, Yuankai Wu, Takanori Ito, Eunice Y. Lee, KeeSeok Lee, Christopher D. Stave, Linda Henry, Scott D. Barnett, Ramsey Cheung, Mindie H. Nguyen
Journal: Journal of Hepatology (2023)
A TNFα/Miz1-positive feedback loop inhibits mitophagy in hepatocytes and propagates non-alcoholic steatohepatitis
Authors: Kangpeng Jin, Yuze Shi, Haitian Zhang, Guangyan Zhangyuan, Fei Wang, Shuo Li, Chen Chen, Jinyao Zhang, Hua Wang, Wenjie Zhang, Beicheng Sun
Journal: Journal of Hepatology (2023)
Periorbital Edema in Dermatomyositis
Authors: Caoilfhionn M Connolly, Lisa Christopher-Stine
Journal: New England Journal of Medicine (2023)

A 61-year-old woman presented with a 6-month history of periorbital swelling and shoulder weakness. The physical examination was notable for erythema of the upper and lower eyelids and substantial periorbital edema.
Collaborative strategies for deploying artificial intelligence to complement physician diagnoses of acute respiratory distress syndrome
Authors: Negar Farzaneh, Sardar Ansari, Elizabeth Lee, Kevin R. Ward, Michael W. Sjoding
Journal: npj Digital Medicine (2023)

Abstract There is a growing gap between studies describing the capabilities of artificial intelligence (AI) diagnostic systems using deep learning versus efforts to investigate how or when to integrate AI systems into a real-world clinical practice to support physicians and improve diagnosis. To address this gap, we investigate four potential strategies for AI model deployment and physician collaboration to determine their potential impact on diagnostic accuracy. As a case study, we examine an AI model trained to identify findings of the acute respiratory distress syndrome (ARDS) on chest X-ray images. While this model outperforms physicians at identifying findings of ARDS, there are several reasons why fully automated ARDS detection may not be optimal nor feasible in practice. Among several collaboration strategies tested, we find that if the AI model first reviews the chest X-ray and defers to a physician if it is uncertain, this strategy achieves a higher diagnostic accuracy (0.869, 95% CI 0.835–0.903) compared to a strategy where a physician reviews a chest X-ray first and defers to an AI model if uncertain (0.824, 95% CI 0.781–0.862), or strategies where the physician reviews the chest X-ray alone (0.808, 95% CI 0.767–0.85) or the AI model reviews the chest X-ray alone (0.847, 95% CI 0.806–0.887). If the AI model reviews a chest X-ray first, this allows the AI system to make decisions for up to 79% of cases, letting physicians focus on the most challenging subsets of chest X-rays.
High baseline tumor burden‐associated macrophages promote an immunosuppressive microenvironment and reduce the efficacy of immune checkpoint inhibitors through the IGFBP2‐STAT3‐PD‐L1 pathway
Authors: Zhaowei Wen, Huiying Sun, Zhihua Zhang, Yannan Zheng, Siting Zheng, Jianping Bin, Yulin Liao, Min Shi, Rui Zhou, Wangjun Liao
Journal: Cancer Communications (2023)

Abstract Background Several clinical studies have uncovered a negative correlation between baseline tumor burden and the efficacy of immune checkpoint inhibitor (ICI) treatment. This study aimed to uncover the specific mechanisms underlying the difference in sensitivity to ICI treatment between tumors with high (HTB) and low (LTB) tumor burden. Methods For in vivo studies, several mouse models of subcutaneous tumors were established, and transcriptome sequencing, immunohistochemistry, and flow cytometry assays were used to detect the immune status in these subcutaneous tumors. For in vitro experiments, co‐culture models, cytokine antibody arrays, western blotting, flow cytometry, and enzyme‐linked immunosorbent assays were used to explore the underlying molecular mechanisms Results We found that MC38 or B16 subcutaneous tumors from the HTB group did not show any response to anti‐programmed cell death protein‐1 (PD‐1) therapy. Through flow cytometry assays, we found that the infiltration with CD8 + T cells was significantly decreased whereas M2‐like macrophages were enriched in subcutaneous tumors of HTB groups compared with those of LTB group. These changes were not affected by the initial number of injected tumor cells or tumor age, nor could they be reversed by surgical tumor reduction. Intraperitoneal colony‐stimulating factor 1 receptor (CSF‐1R) inhibitor PLX3397 injection at different time points of tumor growth only had an effect when administered in the early tumor stage to maintain the “heat” of the tumor microenvironment during the process of tumor growth, thereby achieving a response to ICI treatment when the tumor grew to a large size. Mechanistically, we found that insulin‐like growth factor binding protein 2 (IGFBP2) expression levels were significantly elevated in HTB tumor tissues. IGFBP2 promoted the programmed death‐ligand 1 (PD‐L1) expression in M2‐like macrophages by activating signal transducer and activator of transcription 3 (STAT3), and PD‐L1 + M2‐like macrophages exerted an immunosuppressive effect by inhibiting the proliferation and activation of CD8 + T cells in a PD‐L1‐dependent fashion. Conclusions This study suggested that the low efficacy of ICI treatment in HTB tumors is mainly attributed to the intratumoral accumulation of PD‐L1 + M2‐like macrophages via the IGFBP2‐STAT3‐PD‐L1 signaling pathway and their substantial inhibitory effects on T cell proliferation and activation.
COVID‐19 in early 2023: Structure, replication mechanism, variants of SARS‐CoV‐2, diagnostic tests, and vaccine &amp; drug development studies
Authors: Ilker Polatoğlu, Tulay Oncu‐Oner, Irem Dalman, Senanur Ozdogan
Journal: MedComm (2023)

Coronavirus Disease-19 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome-coronaviruses-2 (SARS-CoV-2), a highly pathogenic and transmissible coronavirus. Most cases of COVID-19 have mild to moderate symptoms, including cough, fever, myalgias, and headache. On the other hand, this coronavirus can lead to severe complications and death in some cases. Therefore, vaccination is the most effective tool to prevent and eradicate COVID-19 disease. Also, rapid and effective diagnostic tests are critical in identifying cases of COVID-19. The COVID-19 pandemic has a dynamic structure on the agenda and contains up-to-date developments. This article has comprehensively discussed the most up-to-date pandemic situation since it first appeared. For the first time, not only the structure, replication mechanism, and variants of SARS-CoV-2 (Alpha, Beta, Gamma, Omicron, Delta, Epsilon, Kappa, Mu, Eta, Zeta, Theta, lota, Lambda) but also all the details of the pandemic, such as how it came out, how it spread, current cases, what precautions should be taken, prevention strategies, the vaccines produced, the tests developed, and the drugs used are reviewed in every aspect. Herein, the comparison of diagnostic tests for SARS-CoV-2 in terms of procedure, accuracy, cost, and time has been presented. The mechanism, safety, efficacy, and effectiveness of COVID-19 vaccines against SARS-CoV-2 variants have been evaluated. Drug studies, therapeutic targets, various immunomodulators, and antiviral molecules applied to patients with COVID-19 have been reviewed.
A novel patient-derived 3D model recapitulates mantle cell lymphoma lymph node signaling, immune profile and in vivo ibrutinib responses
Authors: Ferran Araujo-Ayala, Cèlia Dobaño-López, Juan García Valero, Ferran Nadeu, Fabien Gava, Carla Faria, Marine Norlund, Renaud Morin, Pascale Bernes-Lasserre, Neus Serrat, Heribert Playa-Albinyana, Rubén Giménez, Elías Campo, Jean-Michel Lagarde, Armando López-Guillermo, Eva Gine, Dolors Colomer, Christine Bezombes, Patricia Pérez-Galán
Journal: Leukemia (2023)

Mantle cell lymphoma (MCL), a rare and aggressive B-cell non-Hodgkin lymphoma, mainly develops in the lymph node (LN) and creates a protective and immunosuppressive niche that facilitates tumor survival, proliferation and chemoresistance. To capture disease heterogeneity and tumor microenvironment (TME) cues, we have developed the first patient-derived MCL spheroids (MCL-PDLS) that recapitulate tumor oncogenic pathways and immune microenvironment in a multiplexed system that allows easy drug screening, including immunotherapies. MCL spheroids, integrated by tumor B cells, monocytes and autologous T-cells self-organize in disc-shaped structures, where B and T-cells maintain viability and proliferate, and monocytes differentiate into M2-like macrophages. RNA-seq analysis demonstrated that tumor cells recapitulate hallmarks of MCL-LN (proliferation, NF-kB and BCR), with T cells exhibiting an exhaustion profile (PD1, TIM-3 and TIGIT). MCL-PDLS reproduces in vivo responses to ibrutinib and demonstrates that combination of ibrutinib with nivolumab (anti-PD1) may be effective in ibrutinib-resistant cases by engaging an immune response with increased interferon gamma and granzyme B release. In conclusion, MCL-PDLS recapitulates specific MCL-LN features and in vivo responses to ibrutinib, representing a robust tool to study MCL interaction with the immune TME and to perform drug screening in a patient-derived system, advancing toward personalized therapeutic approaches.
Meiotic Recognition of Evolutionarily Diverged Homologs: Chromosomal Hybrid Sterility Revisited
Authors: Jiri Forejt, Petr Jansa
Journal: Molecular Biology and Evolution (2023)

Abstract Hybrid sterility (HS) is an early postzygotic reproductive isolation mechanism observed in all sexually reproducing species. Infertility of hybrids prevents gene flow between incipient species and leads to speciation. While Drosophila studies have focused almost exclusively on the genic control of HS, two other model species, Mus musculus and budding yeast, provided the first experimental evidence of hybrid sterility governed by the nongenic effects of DNA sequence divergence. Here, we propose that the nongenic effect of increasing DNA divergence between closely related species may impair mutual recognition of homologous chromosomes and disrupt their synapsis. Unsynapsed or mispaired homologs can induce early meiotic arrest, or their random segregation can cause aneuploidy of spermatids and sperm cells. Impaired recognition of homologs may thus act as a universal chromosomal checkpoint contributing to the complexity of genetic control of HS. Chromosomal HS controlled by the Prdm9 gene in mice and HS driven by the mismatch repair machinery in yeast are currently the most advanced examples of chromosomal homology search-based HS. More focus on the cellular and molecular phenotypes of meiosis will be needed to further validate the role of homolog recognition in hybrid sterility and speciation.
Causes of Childhood Blindness in the United States Using the IRIS® Registry (Intelligent Research in Sight)
Authors: Han Woong Lim, Suzann Pershing, Darius M. Moshfeghi, Hwan Heo, Md Enamul Haque, Scott R. Lambert, Suzann Pershing, Leslie Hyman, Julia A. Haller, Aaron Y. Lee, Cecilia S. Lee, Flora Lum, Joan W. Miller, Alice Lorch
Journal: Ophthalmology (2023)